Genomic evolution and virulence association of Clostridioides difficile sequence type 37 (ribotype 017) in China

Abstract

Clostridioides difficile sequence type (ST) 37 (ribotype 017) is one of the most prevalent genotypes circulating in China. However, its genomic evolution and virulence determinants were rarely explored. Whole-genome sequencing, phylogeographic and phylogenetic analyses were conducted for C. difficile ST37 isolates. The 325 ST37 genomes from six continents, including North America (n=66), South America (n=4), Oceania (n=7), Africa (n=9), Europe (n=138) and Asia (n=101), were clustered into six major lineages, with region-dependent distributions, harbouring an array of antibioticresistance genes. The ST37 strains from China were divided into four distinct sublineages, showing five importation times and international sources. Isolates associated with severe infections exhibited significantly higher toxin productions, tcdB mRNA levels, and sporulation capacities (P < 0.001). Kyoto Encyclopedia of Genes and Genomes analysis showed 10 metabolic pathways were significantly enriched in the mutations among isolates associated with severe CDI (P < 0.05). Gene mutations in glycometabolism, amino acid metabolism and biosynthesis virtually causing instability in protein activity were correlated positively to the transcription of tcdR and negatively to the expression of toxin repressor genes, ccpA and codY. In summary, our study firstly presented genomic insights into genetic characteristics and virulence association of C. difficile ST37 in China. Gene mutations in certain important metabolic pathways are associated with severe symptoms and correlated with higher virulence in C. difficile ST37 isolates.

Molecular Epidemiology and Antimicrobial Resistance of Clostridioides difficile in Hospitalized Patients From Mexico

“…However, a moderate agreement was found for rifampicin and an excellent agreement for fusidic acid ( Table 2 ), suggesting the utility of these markers in our community. The tet M gene was a poor predictor for tetracycline susceptibility phenotype, similar to results reported by Xu et al (2021) .…”

Complete Genome Sequencing and Comparative Phenotypic Analysis Reveal the Discrepancy Between Clostridioides difficile ST81 and ST37 Isolates

“…Genomes of C. difficile typically exhibit high levels of diversity and plasticity with low levels of gene conservation ( Knight et al, 2015 ). The distribution of C. difficile ST37 was determined to be region dependent with high sequence diversification based on a large-scale genomic investigation in China ( Xu et al, 2021 ). Herein, isolates belonging to the two sequence types were found to be tightly clustered, possibly owing to a common origin.…”

“…As essential mobile genetic elements, ICEs are responsible for horizontal gene transfer, driving increased genetic diversity and the acquisition of exogenous genes ( He et al, 2010 ). Transposons, including Tn 916 , transposons from the Tn 916 -like family, Tn 5397 , Tn 5397 -like elements, Tn 6002 -like elements, and so on, have been found to be widely dispersed in ST37 isolates ( Xu et al, 2021 ). Herein, nine types of ICEs could be annotated to the genome of these isolates and we selected four as representatives, including, CTn 5 , CTn 6 , Tn 916 , and Tn 6194 -like, on the basis of the most matched ORFs.…”

“…With the exception of CTn 6 , ST81 had all of the transposons found in ST37 but with more insertions and deletions compared with the reference sequences. Tn 916 , a well-known tet (M)-carrying element, is considered to play a key role in tet (M) gene acquisition and tetracycline resistance ( Xu et al, 2021 ). Thus, the ST81 and ST37 isolates displayed similar rates of resistance to tetracycline.…”

“…Whole genome sequencing is commonly used to explore genome evolution and the variability of virulence factors ( Janezic and Rupnik, 2015 ). The genomic features and genetic association with virulence have been previously described for ST37 ( Liu et al, 2020 ; Xu et al, 2021 ), whereas these aspects remain ambiguous for ST81.…”